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21-12-2021 | Rheumatology | News | Article

IL-16 implicated in lupus nephritis pathogenesis

Author:
Laura Cowen

medwireNews: Expression of the proinflammatory cytokine interleukin (IL)-16 strongly correlates with histologic activity in people undergoing treatment for lupus nephritis (LN), shows a longitudinal study of urinary proteomic profiles.

Andrea Fava (Johns Hopkins University, Baltimore, Maryland, USA) and co-investigators say their findings “implicate IL-16 in lupus nephritis pathogenesis designating it as a potentially treatable target and biomarker.”

Fava and team identified 237 protein biomarkers, from a panel of 1000, that were significantly elevated in urine samples taken at the time of the diagnostic renal biopsy from 30 patients with LN relative to samples from seven healthy controls without systemic lupus erythematosus.

Pathway enrichment analysis showed that these proteins were involved in 12 non-overlapping biologic pathways, including those for chemotaxis, neutrophil activation, platelet degranulation, and extracellular matrix organization.

Furthermore, the enriched pathways clustered into two groups, with either intermediate or high abundance. Of note, baseline proteinuria and other parameters were similar between the two clusters, “suggesting that these signatures specifically reflect active biological processes rather than a non-specific increase or decrease of all urine proteins,” the researchers remark.

They found that the majority (80%) of people who later achieved a complete renal response to treatment clustered in the intermediate abundance group, but stress that “[t]he predictive value of this approach needs to be validated in a larger cohort given the small number of responders.”

In terms of renal histology, the researchers observed differential abundance of a number of proteins, particularly IL-16, in people with proliferative (n=14) versus membranous (n=9) LN.

IL-16 levels also most strongly correlated with histologic activity, along with CD163 and transforming growth factor-β, after adjustment for multiple confounders, including proteinuria.

And analysis of samples taken at 3, 6, and 12 months showed that the urinary concentration of these three proteins fell over time in complete and partial responders but not in nonresponders.

Fava and colleagues used immunohistochemical staining of seven LN kidney biopsies to show that IL-16 expression is abundant in interstitial and glomerular cells in proliferative LN and correlates with both urinary IL-16 abundance and histologic activity.

They believe this suggests “that IL-16 is intrarenally produced in proliferative LN and urinary IL-16 reflects the abundance of intrarenal IL-16 positive cells and LN activity.”

Writing in Arthritis & Rheumatology, the authors conclude that their results show “that the pathological processes in LN can be noninvasively captured and monitored over time.”

They add: “Urine proteomics may profoundly change the diagnosis and management of lupus nephritis by noninvasively monitor[ing] active intrarenal biological pathways.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group

Arthritis Rheumatol 2021; doi:10.1002/art.42023

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